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慢性肾脏病中的维生素 B6 代谢——与转硫作用、糖基化终产物和心血管疾病的关系。

Vitamin B6 metabolism in chronic kidney disease--relation to transsulfuration, advanced glycation and cardiovascular disease.

机构信息

Department of Internal Medicine III, University of Jena, Jena, Germany.

出版信息

Nephron Clin Pract. 2010;114(1):c38-46. doi: 10.1159/000245068. Epub 2009 Oct 9.

Abstract

BACKGROUND

Vitamin deficiency is common in chronic kidney disease (CKD). Data on B(6) supply and possible relationships to cardiovascular events (CVE) in CKD are rare. Pyridoxamine exerts inhibitory effects on the formation of advanced glycation endproducts (AGE) implicated in the pathogenesis of CKD and atherosclerosis.

METHODS

In 48 CKD patients at stage 2-4, 72 hemodialysis patients (HD), 38 renal transplant recipients (RTR) and 141 healthy controls (mean age 58 +/- 13, 61 +/- 12, 50 +/- 12 and 54 +/- 16 years, respectively), plasma and red blood cell (RBC) concentrations of pyridoxal-5'-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), pyridoxamine-5'-phosphate (PMP) and of the AGE pentosidine were measured by high-performance liquid chromatography, N(epsilon)-(carboxymethyl)lysine and imidazolone by an ELISA, and total homocysteine and cystathionine by gas chromatography-mass spectrometry.

RESULTS

Despite routine low-dose vitamin supplementation in HD, plasma PLP was decreased in HD (79 +/- 69 nmol/l) compared with CKD stage 2-4 patients (497 +/- 944 nmol/l), RTR (416 +/- 604 nmol/l) and controls (159 +/- 230 nmol/l; p < 0.001). Plasma PA was significantly increased in HD (11,667 +/- 17,871 nmol/l) in comparison with CKD stage 2-4 (435 +/- 441 nmol/l), RTR (583 +/- 668 nmol/l) and controls (46 +/- 49 nmol/l; p < 0.001). B(6) forms were significantly affected by renal function (R = 0.792, p < 0.001 for CKD stage 2-4). There was no relation of vitamers with a history of CVE. Relationships between B(6) forms and AGE (RBC-PMP with pentosidine in CKD stage 2-4: R = -0.351, p < 0.05) were found.

CONCLUSION

HD patients showed a deficiency in PLP in plasma but not in RBC. Prospective trials are needed to elucidate the potential role of elevated PA on cardiovascular and renal outcome in CKD. Vitamin B(6) supplementation might be successful in preventing AGE-related pathologies.

摘要

背景

维生素缺乏在慢性肾脏病(CKD)中很常见。关于 B(6)供应的数据以及其与 CKD 中心血管事件(CVE)的可能关系的数据很少。吡哆胺对涉及 CKD 和动脉粥样硬化发病机制的晚期糖基化终产物(AGE)的形成具有抑制作用。

方法

在 48 名 CKD 患者(2-4 期)、72 名血液透析患者(HD)、38 名肾移植受者(RTR)和 141 名健康对照者(平均年龄分别为 58 +/- 13、61 +/- 12、50 +/- 12 和 54 +/- 16 岁)中,通过高效液相色谱法测量血浆和红细胞(RBC)中的吡哆醛-5'-磷酸(PLP)、吡哆醛(PL)、4-吡啶羧酸(PA)、吡哆胺-5'-磷酸(PMP)和 AGE 戊糖胺,通过 ELISA 测量 N(epsilon)-(羧甲基)赖氨酸和咪唑啉酮,通过气相色谱-质谱法测量总同型半胱氨酸和胱硫醚。

结果

尽管 HD 中常规进行低剂量维生素补充,但与 CKD 2-4 期患者(497 +/- 944 nmol/l)、RTR(416 +/- 604 nmol/l)和对照组(159 +/- 230 nmol/l)相比,HD 患者的血浆 PLP 降低(79 +/- 69 nmol/l;p < 0.001)。与 CKD 2-4 期(435 +/- 441 nmol/l)、RTR(583 +/- 668 nmol/l)和对照组(46 +/- 49 nmol/l)相比,HD 患者的血浆 PA 显著升高(11,667 +/- 17,871 nmol/l;p < 0.001)。B(6)形式受肾功能影响显著(CKD 2-4 期 R = 0.792,p < 0.001)。B 族维生素形式与 CVE 病史无相关性。B(6)形式与 AGE(CKD 2-4 期 RBC-PMP 与戊糖胺:R = -0.351,p < 0.05)之间存在关系。

结论

HD 患者血浆中 PLP 缺乏,但 RBC 中不缺乏。需要前瞻性试验来阐明 PA 升高对 CKD 心血管和肾脏结局的潜在作用。维生素 B(6)补充可能成功预防 AGE 相关的病理变化。

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